Non-small cell lung carcinoma is one of the most frequently occurred
cancers with a very high rate of recurrence. Self-assembly N-(2-hydroxypropyl)
methacrylamide (
HPMA)
micelles and cross-linked
micelles were developed to improve antitumor ability of linear
HPMA copolymer. The characters of
HPMA micelles were investigated and compared using human
non-small cell lung carcinoma 3-D culture model and nude mice xenograft model. Cross-linked
micelles showed highest cytotoxicity on A549 cell monolayers after a short time treatment in vitro. Moreover, both of the two
micelles exhibited better in vitro anti-
tumor activity on A549
tumor spheroids than linear
HPMA conjugates especially the cross-linked
micelles. On BALB/c nude mice bearing A549 xenograft
tumors, the cross-linked
micelles exhibited the greatest
tumor accumulation and the best anti-
tumor activity due to the highly improved stabilities and the more pronounced enhanced permeability and retention (EPR) effect, which were followed by the non-cross-linked
micelles. Meanwhile, neither the two
micelles nor the linear
HPMA copolymers showed significant toxicity on the main organs of mice while free
doxorubicin (DOX) showed obvious
cardiac toxicity. All the results suggested that micellization improved the anti-
tumor activity of
HPMA copolymers on A549 human
non-small cell lung carcinoma, furthermore, cross-linked
HPMA copolymer
micelles with pH-sensitivity and biodegradability showed more excellent anti-
tumor activity.